Conditioned social preference and reward value of activating oxytocin‐receptor‐expressing ventral tegmental area neurons following repeated daily binge ethanol intake. (7th January 2022)

• Record Type: Journal Article
• Authors: Peris, Joanna; Totten, Katye; Montgomery, Darrice; Lester, Hannah; Weatherington, Arnika; Piotrowski, Brian; Sowell, Sam; Doyle, Kristen; Scott, Karen; Tan, Yalun; MacFadyen, Kaley A.; Engle, Hannah; de Kloet, Annette D.; Krause, Eric G.
• Is Part Of: Alcoholism. Volume 46:Number 2(2022)
• Page Start: 194
• Page End: 206
• Publication Date: 2022-01-07
• Subjects: binge ethanol -- oxytocin receptor -- social reward -- ventral tegmental area; Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.14769
• Languages: English
• ISSNs: 0145-6008

Abstract

Abstract: Background: Individuals with alcohol use disorder (AUD) exhibit a disruption of social behavior and dysregulation of oxytocin signaling in the brain, possibly reflecting decreased activation of oxytocin receptors (OxTRs) in reward pathways in response to social stimuli. We hypothesize that daily binge ethanol intake causes a deficit in social reward and oxytocin signaling in the ventral tegmental area (VTA). Methods: After 9 weeks of daily binge ethanol intake (blood ethanol concentration >80 mg%), OxTR‐cre mice underwent conditioned place preference for social reward. Separate groups of mice were tested for the effects of binge ethanol on voluntary social interactions, food reward, locomotion, and anxiety‐like behaviors. A subset of mice underwent transfection of OxTR‐expressing VTA neurons (VTA Oxtr ) with a light‐sensitive opsin, followed by operant training to respond to light delivered to VTA. Results: Ethanol‐naïve male mice increased the time spent on the side previously paired with novel mice while ethanol‐treated mice did not. Binge ethanol did not affect conditioned place preference for food reward in males, but this response was weakened in ethanol‐treated females. Ethanol treatment also caused a sex‐specific impairment of voluntary social interactions with novel mice. There were minimal differences between groups in measures of anxiety and locomotion. Ethanol‐naïve mice had significantly greater operant responding for activation of VTA Oxtr than sham‐transfected mice but ethanol‐treated mice did not. There was no difference in the number of VTA Oxtr after binge ethanol. Conclusions: Daily binge ethanol causes social reward deficits that cannot be explained by nonspecific effects on other behaviors, at least in males. Only ethanol‐naïve mice exhibited positive reinforcement caused by activation of VTA Oxtr while daily binge ethanol did not alter the number of VTA Oxtr in either males or females. Thus, subtle dysregulation of VTA Oxtr function may be related to the social reward deficits caused by daily binge ethanol. Abstract : Daily binge ethanol intake selectively decreases the reward value of social interactions in male mice. This deficit is not due to non‐specific effects on cognitive, locomotor or anxiety‐like behaviors. At the same time, daily binge ethanol decreases positive reinforcement caused by activating VTA neurons that are actively expressing oxytocin receptors, while not affecting the number of those neurons. Thus, subtle dysregulation of oxytocin receptor expression may be related to the social reward deficits caused by daily binge ethanol.